Atrial (ANP) and Brain (BNP) natriuretic peptides protect against the adverse changes in cardiac structure and function, known as cardiac remodelling, that occur during heart disease progression. This cardiac remodelling is largely attributed to the disease state re-activating a poorly-defined fetal gene program. Mice that lack the Npr-1 receptor mediating ANP and BNP bioactivity exhibit cardiac remodelling. We have observed that the number of surviving Npr-1 knockout (KO) embryos declines significantly during gestation and the neonatal period, and propose that the natriuretic peptides play a previously unrecognised role in fetal cardiac development. We compared cardiac anatomy, histology and gene expression of Npr-1 KO and wild-type (WT) hearts at three key time points in cardiac development, 12.5 and 15.5 days post coitum (p.c) and neonatal day one in both male and female mice of each genotype (n=6 per group). Increased heart size was apparent in KO mice from 15.5 days p.c, but cardiac fibrosis was not evident until eight weeks of age. Microarray analysis on 22k Oligo arrays of Npr-1 KO and WT embryos and neonates indicated altered expression (p<0.05) of genes involved in cardiac structure (Myosin light chain, Collagen I & III), developmental axis determination and regulation of transcription (GATA-4 & 6, Mef 2A & 2B, Activin IIB Receptor pathway), myocyte cell proliferation and hypertrophy (ANP, CamK4, MAPKKK5), as well as genes involved in energy utilisation and metabolism (GAPDH, GSK-3B). In summary, in addition to their cardioprotective effects in the adult heart, the natriuretic peptide family appears to interact extensively with several developmental signalling pathways.

Myopia, commonly referred to as short sightedness, is a common cause of visual disability throughout the world and affects 25% of the western population. Myopia causes parallel light to focus in front of the retina. It is usually a consequence of the axial length (AL) of the eye being too long. An association between myopia and glaucoma has been documented. In glaucoma, the pattern electroretinogram (PERG) amplitude is often reduced before it is possible to detect a scotoma in the patient’s visual field.

The aim of our study was to determine whether the AL can also influence the PERG amplitude. Thirty five normal myopic volunteers (mean age = 32 years; SD = 5.5 years) participated in this study which received approval from the Canterbury Ethics Committee. Each volunteer had passed a complete ophthalmic screening examination and had a best corrected visual acuity of 6/9 or better. Only the results of the right eye from each volunteer were included in the statistical analysis.

Our findings confirm a significant correlation between the AL of normal myopic eyeball and the PERG amplitude (correlation coefficient r = -0.42; p < 0.01).

In conclusion, the longer axial length of a myopic eyeball may also be responsible for the reduction of PERG amplitude and therefore needs to be considered when interpreting the PERG results.

Vasovagal syncope (or fainting) is a fall in blood pressure secondary to generalised vasodilation, although the exact mechanism is unknown. This reaction can be reproduced in the laboratory using tilt testing. We hypothesised that during tilt-induced syncope, blood flow to the gut is increased.

We measured superior mesenteric arterial blood velocity using pulsed doppler ultrasound, with blood pressure, heart rate and sympathetic nerve activity continuously in 40 patients. Patients were initially monitored in the horizontal (base-line) position, then at 60 deg head-up tilt until syncope, or for 30 minutes if they tolerated the tilt position. Recordings were made at one minute intervals. The Doppler wave-forms were analysed off-line using running averages to plot a maximum velocity envelope. An area ratio was derived to show blood flow changes in each patient during tilt.

Mean horizontal ratios in 5 syncopal patients were 1.36 ±0.38; after a 10 minute tilt 1.14 ±0.23; and at syncope 15.10 ±5.86. In tilt-tolerant patients horizontal and tilt ratios were 1.38 ±0.22 and 1.56 ±0.31 respectively, and remained constant throughout tilt.

Using running average imaging techniques it is possible to process pulsed Doppler wave-forms and gain consistent data from patients during tilt and tilt syncope. This has allowed us to demonstrate that surprisingly, blood flow velocity is severely decreased during tilt induced syncope.

Stress-induced hyperglycaemia is prevalent in intensive care. Tight glucose control can reduce mortality up to 43% if levels are kept below 6.1 mmol/L. This research develops adaptive control algorithms varying both insulin dose and nutritional inputs for targeted glucose control of critically ill patients

To verify the effectiveness of the protocol, retrospective data from 19 ICU patients were used for test simulations. Results are evaluated against the hospital sliding-scale data recorded and insulin-only adaptive control. Results indicate a 312% increase in time spent in the 4-6mmol/L normal glucose range compared to the standard sliding-scale approach and a 240% increase compared to an insulin-only control algorithm. A normally distributed ±7% sensor error of the standard Glucocard II glucose sensor added a mean variability of 2.9% and standard deviation of 1.7% to the results. Finally, note that this protocol has a 25-30% higher average nutrition input rate than the retrospective data for the patients.

The protocol was clinically tested in the Christchurch ICU in seven 10-hour trials. Glucose targets were achieved 82.5% of the time within the 7% measurement error, with the remainder having a 24.4% mean difference and standard deviation less than 12%. However, for missed targets, the absolute errors range of [0.8, 2.9] mmol/L was very small indicating small errors at low glucose values rather than a failure of the algorithm. Glucose levels at the end of the trial were 40% lower, on average, compared to the starting value. Overall, the protocol is very effective at tight control to 5 mmol/L over a wide range of ICU patients, despite changes in condition, while also providing greater nutritional input.

Critically ill patients often have stress-induced hyperglycaemia and keeping glucose levels below 6.1 mmol/L can reduce mortality by 43%. Computerized protocols are effective but require frequent measurement. This research presents a table-based method suitable for clinical practice. Retrospective data from 19 ICU patients representing a broad range of conditions was used to model insulin-glucose dynamics. The table-based scale and two “standard” sliding scales were tested with this model.

The specialized table can be easily applied by clinical staff and is based on prior computerized trials. It is designed to work using 1-2 hour measurement intervals to minimise clinical effort. The approach varies both insulin dose and nutritional input rate to achieve tight control. The standard sliding scales simply match current glucose level to an insulin dose rate until the next measurement. The two sliding scales represent different levels of aggressiveness in insulin dosing. All scales are simulated using 1, 2 and 4 hour measurement intervals.

Time in the 4-6 mmol/L band increased from 41% to 67% for the specialized table versus the sliding scales. Time above 6 mmol/L went from 56% to 28.5% with no hypoglycaemia recorded. The specialized table matches computerized protocols and also provides greater nutritional input over the patient stay while providing better control. Finally, increasing measurement interval decreases effectiveness of sliding scales 10- 20%. Thus, frequent measurement is critical to maintaining tight control given highly variable patient condition. Clinical testing will be required to validate these results.